Epilepsy affects between 0.5 to 1.0% of the general U.S. population, or well over 2 million people. Approximately 20% of these patients do not respond to the best available treatments and continue to have intractable seizures. The economic effect of these numbers and the overall burden to the U.S. health care system is staggering. Epilepsy management translates to annual financial costs of approximately $12.5 billion. The indirect employment related costs are more substantial and they are based on a survey of about 1200 patients in 18 centers. It is estimated that there is a loss of lifetime earnings of 35% in men and 25% in women. Of the new cases diagnosed every year, 61% have no further seizures after the first year and so their overall costs fell drastically after the initial evaluation. 14% had seizures for a year or two, but then eventually became seizure-free for a whole year. Over 20% of new patients never responded well to treatment and continued to have seizures. Due to the addition of new cases in excess of 0.5 million people with epilepsy are not controlled and continue to have seizures. This emphasizes the importance of seizure detection and control and its relationship to the total medical costs.
Of alternative treatments only brain surgery and vagus nerve stimulator (VNS) are significant. The former treatment option can offer a 50-65% probability of freedom from disabling seizures but is possible in only 8% of patients who continue to have seizures. Brain imaging, EEG and exam provide good prognostic information if surgery is likely to be successful, for example in the case of an accessible brain tumor the outcome is usually good. The option of a seizure detection and control device offers a valuable alternative to surgical treatment since surgery can not be performed in cases of epileptic lesions localized to vital, or “eloquent”, brain areas and it also offers the possibility of empirical treatment with less need to verify that seizures originate in a certain brain lesion. VNS offers only palliative treatment in the best of cases. A third alternative treatment, antiepileptic drugs (AED), is complicated by both short-term and long-term side effects. Among the former are psychomotor slowing and decreased cognition, sleepiness and gait disorders. Long term side effects are well known in the older AED probably these have been on the market for a long enough time that they have been detected and the include: osteoporosis, neuropathies, cerebellar atrophy, retinal damage, liver, pancreas and bone marrow problems. Moreover, these drugs are not recommended for women of child bearing age. An improved seizure detection and control device will eliminate the side effects of drug therapy and make productive, those patients who do not respond to alternative treatments. In addition to these possible beneficial effects an improved seizure detection and control would provide improvement of secondary effects of seizures, like depression and psychosis that affects a majority of patients with epilepsy.
An approach to seizure control is to detect the early onset of a seizure and apply either a drug or electrical stimulus to prevent the imminent seizure. Many studies have been done to attempt to detect the onset of seizures using data recorded from EEG electrodes, which are placed on the skin and are, therefore, non-invasive. These methods have generally failed because the information recorded by EEG electrodes has generally been degraded in space and time because the electrodes are placed on the surface of the skin. While it has been demonstrated that seizures can be predicted using pre-seizure neural data from EEG electrodes, the methods are not very accurate and generally a solution can not be computed in real-time. Computing the solution can take hours to days, by which time the seizure has already occurred.
Recently, it has been shown that imminence of seizure can be detected by measurement and analysis of multiple single neuron action potentials. See Moxon, et al. “Real-time Seizure Detection System using Multiple Single Neuron Recordings,” Proceedings of the 23rd Annual International Conference of the IEEE Engineering in Medicine and Biology Society, Istanbul, Turkey, Oct. 25-28, 2001. (Attached as Appendix A). This article and all other references cited in this application are incorporated by reference as if fully set forth herein. When the correlation between neurons recorded on different sites reaches a critical level, a seizure is imminent. At this point, microstimulation or drug administration can be triggered to prevent the full seizure.
For severe cases of epilepsy, implantable microelectrode devices can accurately detect seizure onset in real-time and report on the state of the future seizures giving time for the patient to react or to implement a strategy to stop the onset of the seizure. For these patients an implantable device is warranted because of the severity of the disease. Since this method requires implanting intracranial electrodes, the method is only appropriate for those patients for which other methods do not work. As stated above, this represents about 20% of the total epilepsy patient population or about 500,000 total patients at the present time.
Implantable stimulating microelectrodes are used frequently and have proven very effective in controlling late stages of Parkinson's disease. Methods are currently being pursued to implant microelectrodes for obesity, depression and various dyskinetic disorders. Recently a quadriplegic spinal cord patient was implanted with microelectrodes to record single neurons to restore motor output from the brain.
Recording single neuron action potentials, or spikes, from the brain is generally performed using an array of microelectrodes. In the past, cables have been used to transmit the analog signals from the microelectrodes to a waveform discriminator that detects a spike and registers the spike time. This cabling system requires that the subject be tethered and this tethering limits the movement of the subject and may cause recording disturbance.
A need exists for an effective seizure detection and control system wherein implanted microelectrodes connect to a device that discriminates single neuron spikes, identifies the spike times and transmits this information telemetrically to a controller that analyzes the spikes, determines whether a seizure is imminent and triggers a stimulus or drug to prevent the seizure. Such a device has applicability not only to epilepsy, but to any other area of controlled neuromodulation.